OP0311 High maternal expression of siglec1 on cd14+ monocytes as a surrogate marker of a type i interferon signature is a risk factor for the development of autoimmune congenital heart block
Authors: AR Lisney, F Szelinski, K Reiter, G Burmester, C Scholz, T Rose, T Dörner
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autoimmune congenital heart block (CHB) is a severe manifestation of neonatal lupus syndrome that is associated with placental transcytosis of maternal autoantibodies directed against the ribonucleoproteins Ro/SS-A and, to a lesser extent, La/SS-B.(1) Around 2/3 of affected mothers are diagnosed with either systemic lupus erythematosus (SLE) or primary Sjögren9s syndrome (pSS),(2) which are both pathogenically driven by an upregulation of type I interferons (IFN).(3) <h3>Objectives</h3> Although the pleiotropic effects of type I IFN on the immune system are well documented, a potential role of type I IFN in the development of CHB has not yet been investigated. This study therefore aimed to compare maternal levels of type I IFN activation in affected and unaffected mothers, in order to provide first insights into a potential role of type I IFN in CHB development. <h3>Methods</h3> Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 15 pregnant women with antibodies against Ro/SS-A but without a CHB complication ("Disease Controls", DC), and another 30 healthy pregnant women without the respective autoantibodies as controls were studied. Plasma levels of IFN-α (ELISA), interferon-gamma induced protein 10 (IP-10) (Bioplex®) and the expression of SIGLEC1 on CD14+ monocytes (flow cytometry) were analysed. <h3>Results</h3> Pregnant females with a CHB complication had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU), compared to the DC group. Receiver operating curve (ROC) analysis between the CHB group and the DC group showed that a SIGLEC1 median fluorescence intensity (MFI) of &gt;904 could distinguish between the groups with a sensitivity of 100% and a specificity of 64%, and a concentration of IFN-α &gt;0.70 pg/ml with a sensitivity of 67% and a specificity of 86%. Healthy pregnant females without the respective autoantibodies had the lowest levels for all three parameters. In a cohort of 5 females, both the expression of SIGLEC1 and plasma levels of IFN-α were reduced by hydroxychloroquine and oral glucocorticoids. <h3>Conclusions</h3> This is the first study to report increased type I IFN activation in pregnant females with a CHB complication. Also, we show here that IFN-α directed therapy, e.g. with hydroxychloroquine, may be especially beneficial in these females. <h3>References</h3> Brito-Zeron P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. Autoimmune congenital heart block: complex and unusual situations. Lupus. 2016; 25(2):116–28. Brito-Zeron P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol. 2015;11(5):301–12. Lopez de Padilla CM, Niewold TB. The type I interferons: Basic concepts and clinical relevance in immune-mediated inflammatory diseases. Gene. 2016;576(1 Pt 1):14–21. <h3>Disclosure of Interest</h3> None declared